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GeneE
3 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
OTULINL
OTU deubiquitinase with linear linkage specificity like
Chromosome 5 Β· 5p15.2
NCBI Gene: 54491Ensembl: ENSG00000145569.7HGNC: HGNC:25629UniProt: Q9NUU6
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ubiquitin-like protein peptidase activityubiquitin bindingprotein deubiquitinationnuclear envelopeasthmachildhood onset asthmarespiratory system diseaseallergic disease
✦AI Summary

OTULINL (FAM105A) is a pseudodeubiquitinase of the OTU family that lacks catalytic deubiquitinase activity despite structural homology to active DUBs 1. Crystal structure analysis reveals critical deficiencies in both the active site and substrate-binding regions that prevent ubiquitin cleavage across all linkage types 1. Unlike its catalytically active paralog OTULIN, OTULINL cannot bind ubiquitin or process ubiquitin chains 1. Instead, OTULINL functions as a protein interaction scaffold, localizing to the endoplasmic reticulum (ER) and nuclear envelope where it associates with proteins involved in membrane trafficking, vesicular transport, and ER/Golgi functions 1. Recent genome-wide association studies identified OTULINL as a novel genetic locus associated with renin-angiotensin-aldosterone system inhibitor-induced angioedema, a serious adverse drug reaction with significant racial disparities 2. This discovery suggests OTULINL may play a role in bradykinin-related pathways implicated in angioedema pathogenesis 2. The functional role of OTULINL likely depends on protein-protein interactions rather than enzymatic activity, reflecting an emerging class of pseudoenzymes with scaffold functions in cellular homeostasis.

Sources cited
1
OTULINL lacks deubiquitinase activity, contains structural deficiencies in active site and substrate binding, cannot bind ubiquitin, and localizes to ER and nuclear envelope
PMID: 31056421
2
OTULINL is a novel genetic locus for RAAS inhibitor-induced angioedema
PMID: 41542693
3
OTULINL is described as a pseudo-DUB related to OTULIN that resides at the endoplasmic reticulum
PMID: 33288901
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜20
asthmaOpen Targets
0.57Moderate
childhood onset asthmaOpen Targets
0.48Moderate
respiratory system diseaseOpen Targets
0.47Moderate
allergic diseaseOpen Targets
0.44Moderate
diabetes mellitusOpen Targets
0.40Weak
type 2 diabetes mellitusOpen Targets
0.37Weak
Abnormal thrombosisOpen Targets
0.35Weak
chronic obstructive pulmonary diseaseOpen Targets
0.35Weak
lower respiratory tract diseaseOpen Targets
0.35Weak
atopic asthmaOpen Targets
0.35Weak
Eczematoid dermatitisOpen Targets
0.34Weak
atopic eczemaOpen Targets
0.34Weak
anaphylaxisOpen Targets
0.23Weak
multinodular goiterOpen Targets
0.16Weak
heart conduction diseaseOpen Targets
0.16Weak
tooth diseaseOpen Targets
0.14Weak
Respiratory insufficiencyOpen Targets
0.11Weak
deep vein thrombosisOpen Targets
0.09Suggestive
alcohol drinkingOpen Targets
0.06Suggestive
placental retentionOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar β†—
Related Genes
USP11Shared pathway100%JOSD1Shared pathway100%USP17L23Shared pathway100%USP54Shared pathway100%JOSD2Shared pathway100%USP31Shared pathway100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
13%
Brain
12%
Ovary
2%
Heart
2%
Liver
1%
Gene Interaction Network
Click a node to explore
OTULINLUSP11JOSD1USP17L23USP54JOSD2USP31
PROTEIN STRUCTURE
Preparing viewer…
PDB6DRM Β· 2.06 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.21LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.94 [0.73–1.21]
RankingsWhere OTULINL stands among ~20K protein-coding genes
  • #13,475of 20,598
    Most Researched23
  • #12,747of 17,882
    Most Constrained (LOEUF)1.21
Genes detectedOTULINL
Sources retrieved3 papers
Response timeβ€”
πŸ“„ Sources
3
1
Ubiquitin-dependent and -independent functions of OTULIN in cell fate control and beyond.
PMID: 33288901
Cell Death Differ Β· 2021
1.00
2
Genetic and Social Determinants of Renin-Angiotensin-Aldosterone System Inhibitor-Induced Angioedema: A Precision Medicine Health Equity Study.
PMID: 41542693
medRxiv Β· 2026
0.67
3
FAM105A/OTULINL Is a Pseudodeubiquitinase of the OTU-Class that Localizes to the ER Membrane.
PMID: 31056421
Structure Β· 2019
0.33